Combining Evolutionary Conservation and Quantum Topological Analyses To Determine Quantum Mechanics Subsystems for Biomolecular Quantum Mechanics/Molecular Mechanics Simulations

Overview

Journal J Chem Theory Comput

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2021 Jun 4

PMID 34087064

Citations 2

Authors

Mark A Hix

Emmett M Leddin

G Andres Cisneros

Affiliations

Soon will be listed here.

Abstract

Selection of residues and other molecular fragments for inclusion in the quantum mechanics (QM) region for QM/molecular mechanics (MM) simulations is an important step for these calculations. Here, we present an approach that combines protein sequence/structure evolution and electron localization function (ELF) analyses. The combination of these two analyses allows the determination of whether a residue needs to be included in the QM subsystem or can be represented by the MM environment. We have applied this approach on two systems previously investigated by QM/MM simulations, 4-oxalocrotonate tautomerase (4OT) and ten-eleven translocation-2 (TET2), that provide examples where fragments may or may not need to be included in the QM subsystem. Subsequently, we present the use of this approach to determine the appropriate QM subsystem to calculate the minimum energy path (MEP) for the reaction catalyzed by human DNA polymerase λ (Polλ) with a third cation in the active site. Our results suggest that the combination of protein evolutionary and ELF analyses provides insights into residue/molecular fragment selection for QM/MM simulations.

Citing Articles

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